Implantable neural stimulator with mode switching

ABSTRACT

Various aspects of the present subject matter relate to an implantable device. Various device embodiments comprise at least one port to connect to at least one lead with at least electrode, stimulation circuitry connected to the at least one port and adapted to provide at least one neural stimulation therapy to at least one neural stimulation target using the at least one electrode, sensing circuitry connected to the at least one port and adapted to provide a sensed signal, and a controller connected to the stimulation circuitry to provide the at least one neural stimulation therapy and to the sensing circuitry to receive the sensed signal. In response to a triggering event, the controller is adapted to switch between at least two modes. Other aspects and embodiments are provided herein.

CLAIM OF PRIORITY

This application is a continuation of U.S. application Ser. No.16/597,620, filed Oct. 9, 2019, which is a continuation of U.S.application Ser. No. 15/342,687, filed Nov. 3, 2016, now issued as U.S.Pat. No. 10,493,280, which continuation of U.S. application Ser. No.14/318,785, filed Jun. 30 2014, now issued as U.S. Pat. No. 9,486,631,which continuation of U.S. application Ser. No. 13/909,777, filed Jun.4, 2013, now issued as U.S. Pat. No. 8,768,456, which is a division ofU.S. application Ser. No. 11/137,038, filed May 25, 2005, now issued asU.S. Pat. No. 8,473,049, each of which is hereby incorporated byreference in its entirety.

TECHNICAL FIELD

This application relates generally to medical devices and, moreparticularly, to implantable devices capable of providing neuralstimulation.

BACKGROUND

Neural stimulation has been the subject of a number of studies and hasbeen proposed for several therapies. Direct electrical stimulation ofparasympathetic nerves can activate the baroreflex, inducing a reductionof sympathetic nerve activity and reducing blood pressure by decreasingvascular resistance. Sympathetic inhibition, as well as parasympatheticactivation, have been associated with reduced arrhythmia vulnerabilityfollowing a myocardial infarction, presumably by increasing collateralperfusion of the acutely ischemic myocardium and decreasing myocardialdamage. Modulation of the sympathetic and parasympathetic nervous systemwith neural stimulation has been shown to have positive clinicalbenefits, such as protecting the myocardium from further remodeling andpredisposition to fatal arrhythmias following a myocardial infarction.

SUMMARY

Various aspects of the present subject matter relate to an implantabledevice. Various device embodiments comprise at least one port to connectto at least one lead with at least electrode, stimulation circuitry,sensing circuitry and a controller. The stimulation circuitry isconnected to the at least one port and adapted to provide at least oneneural stimulation therapy to at least one neural stimulation targetusing the at least one electrode. The sensing circuitry is connected tothe at least one port and adapted to provide a sensed signal. Thecontroller is connected to the stimulation circuitry to provide the atleast one neural stimulation therapy and to the sensing circuitry. Inresponse to a triggering event, the controller is adapted to switchbetween at least two modes.

In response to a triggering event, the controller of various deviceembodiments is adapted to switch between at least two modes selectedfrom the group consisting of a stimulation and sensing mode, astimulation mode, and a sensing mode. In the stimulation and sensingmode, the neural stimulation therapy is provided using a sensed signal.In the stimulation mode, the neural stimulation therapy is providedwithout using the sensed signal. In the sensing mode, the neuralstimulation therapy is not provided to the neural stimulation target.

In response to a triggering event, the controller of various deviceembodiments is adapted to switch between at least two modes to switchneural stimulation targets. In response to a triggering event, thecontroller of various device embodiments is adapted to switch between atleast two modes to switch sensing sites from which to provide the sensedsignal, to switch sensed parameters used to provide the sensed signal,or to switch both sensing sites and sensed parameters.

Various system embodiments comprise at least one port to connect to atleast one lead with at least electrode, at least one stimulation circuitconnected to the at least one port and adapted to provide at least oneneural stimulation therapy to at least one neural stimulation target andto provide a cardiac rhythm management (CRM) therapy using the at leastone electrode, at least one sensing circuit connected to the at leastone port and adapted to provide a sensed signal, and a controllerconnected to the at least one stimulation circuit to provide the atleast one neural stimulation therapy and the CRM therapy and to thesensing circuitry. In response to a triggering event the controller isadapted to switch between at least two modes selected from the groupconsisting of a neural stimulation therapy mode, a CRM therapy mode, anda neural stimulation and CRM therapy mode. In the neural stimulationtherapy mode, the neural stimulation therapy is provided to the neuraltarget. In the CRM therapy mode, the CRM therapy is provided. In theneural stimulation and CRM therapy mode, the neural stimulation therapyis provided to the neural stimulation target and the CRM therapy isprovided.

In various device embodiments, the controller is adapted to operate thedevice in at least two modes and to switch modes in response to atriggering event. The at least two modes are provided in at least oneset of modes selected from the group consisting of a set of operationmodes, a set of stimulation site modes and a set of feedback modes. Insome embodiments, the group further consists of a set of therapy modessuch that the device is able to switch between or among two or moretherapy modes. Examples of operation modes includes a mode to provideneural stimulation and sensing, a mode to provide neural stimulationwithout sensing, and a mode to provide sensing without neuralstimulation. Examples of stimulation site modes includes a mode toprovide neural stimulation to a first neural stimulation site(s) ortarget(s) and a mode to provide neural stimulation to a second neuralstimulation site(s) or target(s). Examples of feedback modes includes amode to sense from a first site and a mode to sense from a second site,and also includes a mode to sense a first parameter and a mode to sensea second parameter. Examples of therapy modes include neural stimulationtherapy, CRM therapy, drug therapy, and combinations thereof.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects will be apparent to persons skilled in the art upon reading andunderstanding the following detailed description and viewing thedrawings that form a part thereof, each of which are not to be taken ina limiting sense. The scope of the present invention is defined by theappended claims and their equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an embodiment of a system with an implantable medicaldevice (IMD).

FIG. 2 illustrates an embodiment of an implantable neural stimulator(NS) device such as can be incorporated as the IMD in the system of FIG.1.

FIG. 3 illustrates a system diagram of an implantable medical deviceembodiment configured for multi-site stimulation and sensing.

FIG. 4 illustrates an embodiment of an implantable medical device (IMD)such as shown in FIG. 1 having a neural stimulation (NS) component andcardiac rhythm management (CRM) component.

FIG. 5 illustrates a system including a patient-actuated externaldevice, a magnet, an implantable neural stimulator (NS) device and animplantable cardiac rhythm management (CRM) device, according to variousembodiments of the present subject matter.

FIG. 6 illustrates an embodiment of CRM device, such as can be used inthe system of FIG. 5.

FIG. 7 illustrates an implantable medical device (MID) such as shown inFIG. 1 having a neural stimulation (NS) component, a cardiac rhythmmanagement (CRM) component, and a drug delivery component, according tovarious embodiments of the present subject matter.

FIG. 8 illustrates one embodiment of a drug delivery microchip for usein one embodiment of a drug-eluting intravascular device.

FIG. 9 illustrates one embodiment of a drug delivery microchip capableof delivering different drugs and different dosages of the drugs.

FIG. 10 illustrates a patient-actuated programmer, such as the externalpatient-actuated device illustrated in the system of FIG. 1, or otherexternal device to communicate with the implantable medical device(s),according to various embodiments of the present subject matter.

FIG. 11 illustrates an embodiment of a responsive relationship of an IMDcontroller to a triggering event.

FIG. 12 illustrates an embodiment of a controller capable of switchingmodes within a set of operation modes, a set of stimulation site modes,and a set of feedback modes.

FIG. 13 illustrates an embodiment of a controller capable of switchingmodes within a set of operation modes, a set of stimulation site modes,a set of feedback modes, and a set of therapy modes.

DETAILED DESCRIPTION

The following detailed description of the present subject matter refersto the accompanying drawings which show, by way of illustration,specific aspects and embodiments in which the present subject matter maybe practiced. These embodiments are described in sufficient detail toenable those skilled in the art to practice the present subject matter.Other embodiments may be utilized and structural, logical, andelectrical changes may be made without departing from the scope of thepresent subject matter. References to “an”, “one”, or “various”embodiments in this disclosure are not necessarily to the sameembodiment, and such references contemplate more than one embodiment.The following detailed description is, therefore, not to be taken in alimiting sense, and the scope is defined only by the appended claims,along with the full scope of legal equivalents to which such claims areentitled.

The present subject matter relates to an implantable device thatprovides neural stimulation. In various embodiments, the device alsoprovides neural sensing. In addition to neural stimulation therapy,various device embodiments are adapted to provide cardiac rhythmmanagement (CRM) therapy such as pacing, defibrillation, cardiacresynchronization therapy (CRT) or a combination of pacing,defibrillation and CRT. In addition to neural stimulation therapy,various device embodiments are adapted to provide drug therapy. Someembodiments are adapted to provide various combinations of neuralstimulation therapy, CRM therapy and drug therapy. Some therapeutic modeswitches include switching among CRM therapies to treat variousconditions such as atrial fibrillation, bradycardia and ventriculartachycardia.

The device operates using at least two modes, and has the capability toswitch between different modes in response to a triggering event. Avariety of mode types are capable of being switched. Some embodimentschange modes within a set of operation modes. For example, the devicedetects the presence of an unacceptably high level of electricalinterference, and switches to a “stimulate only” mode in which neuralsensing is disabled, or to a “sense only” mode in which neuralstimulation is disabled. Some embodiments change modes to change thesite or sites of neural stimulation. For example, the device reverts toan alternate lead or electrode in response to a detected electrodefailure. Some embodiments change modes within a set of feedback modes tochange sensing sites and/or sensed parameters. Some embodiments areadapted to switch between or among various combinations of neuralstimulation therapy, CRM therapy, and drug therapy.

The triggering event to switch modes can be automatic orpatient-actuated. Examples of patient-actuated triggers include a magnetplaced proximate to the implantable device and an external controllerunit. For example, some device embodiments switch to a “sense only” modein response to an external magnet, providing an emergency shut-offmechanism. Some device embodiments toggle between two or among three ormore different modes of operation in response to an external magnet,Some device embodiments allow the user (e.g. patient) to select the modeof operation with an external controller unit. An example of anautomatic triggering event includes detected noise, where the devicedetects the presence of an unacceptably high level of electricalinterference, and switches to a “stimulate only” mode in which neuralsensing is disabled, or to a “sense only” mode in which neuralstimulation is disabled.

FIG. 1 illustrates an embodiment of a system 100 with an implantablemedical device (IMD) 101. The IMD is adapted to switch modes in responseto a triggering event. According to various embodiments, the triggeringevent is an automatic event, a patient-actuated event, or a combinationof an automatic and patient-actuated events. Examples of automatictriggering events include a detected device change such as a detectedelectrode failure, an End Of Life (EOL) determination for a battery topower the device, a detected lead failure, an environmental change likea detected electrical interference that is capable of interfering withthe sensed signal or the application of another therapy capable ofinterfering with the sensed signal. Automatic triggering events can alsoinclude a detected physiologic change such as a detected change in heartrate, a detected arrhythmia, a detected change in a respiratory rate, adetected change in neural traffic, a detected change in blood pressure,and a detected change in activity. Automatic triggering events can alsobe based on a timer or clock, such as a device with a controller andtimer adapted to follow a circadian rhythm when switching modes.Examples of patient-actuated triggers include an external magnet 102used to actuate a switch (e.g. reed switch) in the implantable device toswitch modes, and a patient-actuated external programmer 103 thatenables the patient to selectively choose the mode to which the deviceshould switch.

FIG. 1 also illustrates the IMD 101 communicating with an externaldevice 103 such as a patient-actuated device capable of being used tochange modes in the IMD 101. A programmer, capable of providing allprogramming functions, including mode switching, can also be used tocommunicate with the IM D. The patient-actuated device can be astand-alone device designed to only provide the desired mode switchingcapabilities, or can be integrated into other devices. An example of apatient-actuated device includes a personal digital assistant or otherelectronic device such as would be used in an advanced patientmanagement (APM) system, which can organize and perform calculationsbased on recorded data, and later provide the data to a programmer.

FIG. 2 illustrates an embodiment of an implantable neural stimulator(NS) device 201 such as can be incorporated as the IMD 101 in the system100 of FIG. 1. The illustrated neural stimulator 201 includes controllercircuitry 204 connected to a memory 205, a sensor 206, neuralstimulation circuitry 207, and a transceiver 208. An electrode 209 isconnected to the stimulator circuitry 207 via a port 209A. The memoryincludes instructions or algorithms operated on by the controller andfurther includes parameters for use in the algorithms to provide thedesired neural stimulation therapy. These instructions and parameterscooperate to operate the device in a mode. The device can be operated indifferent modes by operating on different instructions and/orparameters. Some embodiments use the sensor, such as a neural sensor orother physiologic sensor like a heart rate sensor, to provide feedbackfor the neural stimulation. The stimulator circuitry is adapted toadjust parameters of the neural stimulation signal transmitted to theelectrode. According to various embodiments, one or more of theamplitude, the frequency, the morphology and the burst timing (frequencyand duration of bursts) are capable of being adjusted. Amagnetic-actuated switch 210, such as a reed switch, is connected to thecontroller for use to receive a user-provided trigger (e.g. flux fromthe external magnet) to switch modes. Modes can be switched viacommunications received through the transceiver 208 from the externaldevice or can be automatically switched, such as if mode changes arebased on a clock or other feedback. Historical data for mode switchingevents can be saved in memory 205. The external device can access thememory to display the data regarding the switching events, or canotherwise process the data for a variety of purposes.

FIG. 3 illustrates a system diagram of an implantable medical deviceembodiment configured for multi-site stimulation and sensing. Thisdiagram provides another example of an IMD 301 capable of performing anumber of neural stimulation and CRM therapies. Pacing, as used in thediscussion of this figure, relates to electrical stimulation. In variousembodiments, the stimulation for a given channel includes stimulation tocapture myocardia, neural stimulation or both pacing and neuralstimulation. Three examples of sensing and pacing channels aredesignated “A” through “C”, and such channel can be used to stimulate aright atrium, a right ventricle and a left ventricle, for example. Theillustrated channels comprise bipolar leads with ring electrodes 311A-Cand tip electrodes 312A-C, sensing amplifiers 313A-C, pulse generators314A-C, and channel interfaces 315A-C. Each of these channels includes astimulation channel extending between the pulse generator the electrodeand a sensing channel extending between the sense amplifier and theelectrode. The channel interfaces 315A-C communicate bidirectionallywith microprocessor 316, and each interface may includeanalog-to-digital converters for digitizing sensing signal inputs fromthe sensing amplifiers and registers that can be written to by themicroprocessor in order to output pacing pulses, change the pacing pulseamplitude, and adjust the gain and threshold values for the sensingamplifiers. The sensing circuitry 313A-C detects a chamber sense, eitheran atrial sense or ventricular sense, when an electrogram signal (i.e.,a voltage sensed by an electrode representing cardiac electricalactivity) generated by a particular channel exceeds a specifieddetection threshold. Algorithms, including a number of adjustableparameters, used in particular modes can employ such senses to triggeror inhibit stimulation, and the intrinsic atrial and/or ventricularrates can be detected by measuring the time intervals between atrial andventricular senses, respectively.

The switching network 317 is used to switch the electrodes to the inputof a sense amplifier in order to detect intrinsic cardiac activity andto the output of a pulse generator in order to deliver stimulation. Theswitching network also enables the device to sense or stimulate eitherin a bipolar mode using both the ring and tip electrodes of a lead or ina unipolar mode using only one of the electrodes of the lead with thedevice housing or can 318 serving as a ground electrode or anotherelectrode on another lead serving as the ground electrode. A shock pulsegenerator 319 is also interfaced to the controller for delivering adefibrillation shock via a pair of shock electrodes 320 to the atria orventricles upon detection of a shockable tachyarrhythmia, Channelinterface 321 and neural stimulation pulse generator 322 provide aconnection between the microprocessor and the switch to deliver neuralstimulation using the neural stimulation electrode 323, Channelinterface 324 and sense amplifier 325 provide a connection between themicroprocessor and the switch to receive a sensed signal from a sensor326 for use to provide feedback for therapies such as a neuralstimulation therapy.

The controller or microprocessor controls the overall operation of thedevice in accordance with programmed instructions and a number ofadjustable parameters stored in memory 327, including controlling thedelivery of stimulation via the channels, interpreting sense signalsreceived from the sensing channels, and implementing timers for definingescape intervals and sensory refractory periods. The controller iscapable of operating the device in a number of programmed stimulationmodes which define how pulses are output in response to sensed eventsand expiration of time intervals. Most pacemakers for treatingbradycardia are programmed to operate synchronously in a so-calleddemand mode where sensed cardiac events occurring within a definedinterval either trigger or inhibit a pacing pulse. Inhibited stimulationtriodes utilize escape intervals to control pacing in accordance withsensed intrinsic activity such that a stimulation pulse is delivered toa heart chamber during a cardiac cycle only after expiration of adefined escape interval during which no intrinsic beat by the chamber isdetected. Escape intervals for ventricular stimulation can be restartedby ventricular or atrial events, the latter allowing the pacing to trackintrinsic atrial beats. A telemetry interface 328 is also provided whichenables the controller to communicate with an external programmer orremote monitor.

FIG. 4 illustrates an embodiment of an implantable medical device (IMD)401 such as shown at 101 in FIG. 1 having a neural stimulation (NS)component 429 and cardiac rhythm management (CRM) component 430. Theillustrated device 401 includes a controller 416 and a memory 427.According to various embodiments, the controller includes hardware,software, or a combination of hardware and software to perform theneural stimulation and CRM functions. For example, the programmedtherapy applications, including various mode in which the device canoperate, discussed in this disclosure are capable of being stored ascomputer-readable instructions embodied in memory and executed by aprocessor. According to various embodiments, the controller includes aprocessor to execute instructions embedded in memory to perform theneural stimulation and CRM functions. The illustrated device 401 furtherincludes a transceiver 428 and associated circuitry for use tocommunicate with a programmer or another external or internal device.Various embodiments include a telemetry coil.

The CRM therapy section 430 includes components, under the control ofthe controller, to stimulate a heart and/or sense cardiac signals usingone or more electrodes. The CRM therapy section includes a pulsegenerator 431 for use to provide an electrical signal through anelectrode to stimulate a heart, and further includes sense circuitry 432to detect and process sensed cardiac signals. An interface 433 isgenerally illustrated for use to communicate between the controller 416and the pulse generator 431 and sense circuitry 432. Three electrodesare illustrated as an example for use to provide CRM therapy. Ports inthe device provides signal channels from the device to the electrodes.The present subject matter is not limited to a particular number ofelectrode sites. Each electrode may include its own pulse generator andsense circuitry. However, the present subject matter is not so limited.The pulse generating and sensing functions can be multiplexed tofunction with multiple electrodes.

The NS therapy section 429 includes components, under the control of thecontroller, to stimulate a neural stimulation target and/or senseautonomic nervous system (ANS) parameters associated with nerve activityor surrogates of ANS parameters such as blood pressure and respiration.Three interfaces 434 are illustrated for use to provide ANS therapy.However, the present subject matter is not limited to a particularnumber interfaces, or to any particular stimulating or sensingfunctions. Pulse generators 435 are used to provide electrical pulsesthrough a port to an electrode for use to stimulate a neural stimulationsite. According to various embodiments, the pulse generator includescircuitry to set, and in some embodiments change, the amplitude of thestimulation pulse, the frequency of the stimulation pulse, the burstfrequency of the pulse, and the morphology of the pulse such as a squarewave, triangle wave, sinusoidal wave, and waves with desired harmoniccomponents to mimic white noise or other signals. Sense circuits 436 areused to detect and process signals from a sensor, such as a sensor ofnerve activity, blood pressure, respiration, and the like. Theinterfaces 434 are generally illustrated for use to communicate betweenthe controller 416 and the pulse generator 435 and sense circuitry 436.Each interface, for example, may be used to control a separate lead.Various embodiments of the NS therapy section only include a pulsegenerator to stimulate a neural stimulation target.

According to various embodiments, the lead(s) and the electrode(s) onthe leads are physically arranged with respect to the heart in a fashionthat enables the electrodes to properly transmit pulses and sensesignals from the heart, and with respect to neural targets to stimulate,and in some embodiments sense neural traffic from, the neural targets.Examples of neural targets include both efferent and afferent pathways,such as baroreceptors, nerve trunks and branches such as the vagusnerve, and cardiac fat pads, to provide a desired neural stimulationtherapy. As there may be a number of leads and a number of electrodesper lead, the configuration can be programmed to use a particularelectrode or electrodes.

The leads of the device include one or more leads to provide CRMtherapy, such as atrial pacing, right and/or left ventricular pacing,and/or defibrillation. The device also contains at least one neuralstimulation lead which is placed in an appropriate location. Someembodiments perform neural stimulation and CRM therapy using the samelead. Examples of neural stimulation leads include: an expandablestimulation lead placed in the pulmonary artery in proximity of a highconcentration of baroreceptors; an intravascularly-fed lead placedproximate to a cardiac fat pad to transvascularly stimulate the fat pad;an epicardial lead with an electrode placed in or proximate to the fatpad; a cuff electrode placed around the aortic, carotid, or vagus nerve;and an intravascularly-fed lead placed to transvascularly stimulate theaortic, carotid or vagus nerve. Other lead placements to stimulate otherneural targets may be used.

The controller controls delivery of the electrical pulses, and isadapted to operate the device in a number of different modes. Forexample various embodiments switch between modes selected from the groupconsisting of a set of operation modes, a set of stimulation site modesand a set of feedback modes. In some embodiments, the group furtherconsists of a set of therapy modes such that the device is able toswitch between or among two or more therapy modes. Examples of operationmodes includes a mode to provide neural stimulation and sensing, a modeto provide neural stimulation without sensing, and a mode to providesensing without neural stimulation. Examples of stimulation site modesincludes a mode to provide neural stimulation to a first neuralstimulation site(s) or target(s) and a mode to provide neuralstimulation to a second neural stimulation site(s) or target(s).Examples of feedback modes includes a mode to sense from a first siteand a mode to sense from a second site, and also includes a mode tosense a first parameter and a mode to sense a second parameter. Examplesof therapy modes include neural stimulation therapy. CRM therapy, drugtherapy, and combinations thereof. In addition, various embodiments arealso able to switch between various CRM therapy modes, such as atrialpacing (AGO, AAI), ventricular pacing (VVI, VOO), and or dual chamberpacing (DDI, DDD, VDD), for example. Additionally, changing modesincludes changing parameters for a particular pacing mode, such as baserate, upper rate, AV interval, ventricular refractory and ventricularblanking in a DDD pacing mode.

The illustrated device 401 in FIG. 4 includes a switch 437, such as areed switch, adapted to be actuated by magnetic flux from an externalmagnet positioned proximate to the device 401. The controller and switchare adapted to switch modes when magnetic flux actuates the switch. Invarious embodiments, a patient actuated programmer communicates with thecontroller through the transceiver to change modes. In variousembodiments, the controller automatically changes the modes using, forexample, a feedback signal or a timer. Historical data for modeswitching events can be saved in memory 427. The external device canaccess the memory to display the data regarding the switching events, orcan otherwise process the data for a variety of purposes.

FIG. 5 illustrates a system 538 including a patient-actuated externaldevice 539, a magnet 540, an implantable neural stimulator (NS) device541 and an implantable cardiac rhythm management (CRM) device 542,according to various embodiments of the present subject matter. Variousaspects involve a method for communicating between an NS device and aCRM device or other cardiac stimulator. This communication allows one ofthe devices 541 or 542 to deliver more appropriate therapy (i.e. moreappropriate NS therapy or CRM therapy) based on data and/orcommunication signals received from the other device. Some embodimentsprovide on-demand communications. The illustrated NS device and the CRMdevice are capable of wirelessly communicating with each other, and theprogrammer is capable of wirelessly communicating with at least one ofthe NS and the CRM devices. For example, various embodiments usetelemetry coils to wirelessly communicate data and instructions to eachother. In other embodiments, communication of data and/or energy is byultrasonic means. In some embodiments, a lead provides a hardwiredcommunication path between the two devices.

FIG. 6 illustrates an embodiment of CRM device 642, such as can be usedat 542 in the system of FIG. 5. The illustrated device 642 includes acontroller 643 connected to a memory 644. The figure further illustrateselectrodes 645A and 645B connected to the device. According to theillustration, the electrodes 645A and 645B are connected to sensemodules 646A and 646B to sense electrical signal at the electrode, andpulse generators 647A and 647B to generate stimulation signals to theelectrodes. The controller 643 is connected to the sense modules 646Aand 646B and the pulse generator modules 647A and 647B via interfaces648A and 648B.

The memory includes data and instructions. The controller is adapted toaccess and operate the instructions to perform various functions withinthe device, including programmed. CRM therapies. The memory 644 includesa plurality of parameters that are used to control the delivery of thetherapy using a number of modes. A transceiver 649 is connected to thecontroller 643, The CRM device is capable of wireless communicating withan external device, for example, using the transceiver 649. For example,various embodiments use telemetry coils to wirelessly communicate dataand instructions. In other embodiments, communication of data and/orenergy is by ultrasonic means.

FIG. 7 illustrates an implantable medical device (IMD) 701 such as shownat 101 in FIG. 1 having a neural stimulation (NS) component 734, acardiac rhythm management (CRM) component 735, and a drug deliverycomponent 750, according to various embodiments of the present subjectmatter. Examples of a NS component 734 and a CRM component 735 areillustrated in FIG. 4 at 429 and 430, respectively. The illustrated IMD701 further includes a controller 716 connected to the therapycomponents 734, 735 and 750 to control the delivery of the therapies,and also includes a memory 732 to store instructions and data, atransceiver 733, and a magnetic-actuated switch, such as a reed switch737. The drug delivery component 750 includes an interface 751 toprovide an operable connection between the controller 716 and achronically-implanted drug delivery device 752.

The device is capable of operating in different modes, and switchingbetween or among two or more modes in response to a triggering event.The triggering event can be automatic. Examples of automatic triggeringevent include a timer or feedback signals from various sensors. Thetriggering event can be patient-actuated. One example of apatient-actuated triggering event includes a magnet positioned proximateto the reed switch 737 to toggle the device between or among thedifferent modes. Another example of a patient-actuated triggering eventincludes a patient-actuated programmer that wirelessly communicates withthe device through the transceiver 733 to change modes of operation. Invarious embodiments, the IMD 701 is adapted to respond to a triggeringevent by changing therapy modes among a neural stimulation therapy, aCRM therapy, a drug therapy, and various combinations thereof.

One embodiment of the drug delivery device carries the drug between asubstructure and an electro-erodible overcoat layer; and anotherembodiment of the device carries the drug using a drug delivery “chip”that is separately prepared and subsequently attached to the device. Thedrug is released from the drug delivery chip through an electro-erodiblerelease mechanism. Progressive drug release is provided by wells orregions that are selectively opened by explicitly addressing a givenwell or region, or by a more generalized progressive erosion of atapered thickness electro-erodible overcoat layer. The erosion processcan be open-loop where a well understood time-erosion behavior is known,or can be closed-loop where the erosion progress is monitored using theknown relationship among current, voltage and erosion profile. Eitherprocess provides control of the eroded capping layer and consequent drugrelease.

One embodiment of the drug release chip includes an array of well-likestructures constructed so as to laterally isolate one well from anotherwell so that one well is able to be selectively exposed using anelectro-erodible process, for example, to deliver a specific drug typeand drug dose. An electrically insulating layer covers the well(s) andthe surrounding regions. One or more drugs are contained within thewell(s). A cap layer of electro-erodible material covers the well(s).The electro-erodible material is non-toxic to the host biosystem bothbefore and after electro erosion. One example of an electro-erodiblematerial is gold. The connections and cap layer can be patterned toallow individual well caps to be selected for electro-erosion usingaddressing logic. An electrically insulating, passivation coveringinsulates all interconnections except the intended electro-erosionregion over and perhaps immediately around the drug release well.Alternatively, one or more thickness-graded capping layer(s) areselectively and progressively electro-eroded resulting in controlledprogressive exposure of wells in the thinner capped region first. Invarious embodiments, a current, for a voltage-activated electro-erosionprocess, or a developed potential, for a current-activatedelectro-erosion process, are monitored to control the electro-erosionprocess.

FIG. 8 illustrates one embodiment of a drug delivery microchip 852 foruse in one embodiment of a drug-eluting intravascular device. Accordingto this embodiment, a silicon substrate 853 is formed with voids, wellsor micro-reservoirs 854. These micro-reservoirs 854 have a sufficientsize, are appropriately lined and are otherwise adapted to store anactive substance (e.g. drug) to be released into a biosystem. A coating855 is formed over the silicon substrate. Electro-erodible caps 856 areformed in the coating over the wells such that, upon being eroded, anopening is formed between the well and the surrounding biosystem. Atleast one cathode 857 and least one anode 858 are formed in coating 855.According to one embodiment, the at least one anode forms the electroerodible cap 856, Wiring 859 is used to control, or address, the anodeto be electro eroded.

FIG. 9 illustrates one embodiment of a drug delivery microchip 952capable of delivering different drugs and different dosages of thedrugs. The wells within the microchip are addressable; that is,addressable control lines are used to select the wells Orwell-combinations whose caps 956 are to be electro eroded to elute theactive substance contained therein. In the illustrated electrodeconfiguration, there are five sets of one well, five sets of five wellsand two sets of two wells. The different sized sets provide differentdelivery dosages. Alternatively, the physical size of the wells themselfare used to control the delivery dosage. Additionally, different drugtypes are able to be stored in the different sets of wells, such that adesired drug among several is able to be dispensed upon the detection ofa particular event.

FIG. 10 illustrates a patient-actuated programmer 1003, such as theexternal patient-actuated device 103 illustrated in the system of FIG.1, or other external device to communicate with the implantable medicaldevice(s), according to various embodiments of the present subjectmatter. An example of an external device includes Personal DigitalAssistants (PDAs) or personal laptop and desktop computers in anAdvanced Patient Management (APM) system. The illustrated deviceincludes controller circuitry 1060 and a memory 1061. The controllercircuitry is capable of being implemented using hardware, software, andcombinations of hardware and software. For example, according to variousembodiments, the controller circuitry includes a processor to performinstructions embedded in the memory to perform a number of functions,including communicating data and/or programming instructions to theimplantable devices. According to some embodiments, such instructionsinclude instructions for the device to change modes. The illustrateddevice 1003 further includes a transceiver 1062 and associated circuitryfor use to communicate with an implantable device. Various embodimentshave wireless communication capabilities. For example, variousembodiments of the transceiver and associated circuitry include atelemetry coil for use to wirelessly communicate with an implantabledevice. The illustrated device 1003 further includes a display 1063,input/output (I/O) devices 1064 such as a display, keyboard,mouse/pointer and/or touch screen, and a communications interface 1065for use to communicate with other devices, such as over a communicationnetwork. The patient-actuated device is able to communicate a triggercommand to the IMD to switch to another mode of operation. In anembodiment of the patient-actuated programmer, the instructionscontained in memory and operated on by the controller are appropriate toprovide a user-friendly interface, with appropriate logical security toprevent inappropriate mode changes, to allow the user to change orotherwise select the modes for the IMD.

FIG. 11 illustrates an embodiment of a responsive relationship of an IMDcontroller to a triggering event. The illustration includes a controller1104 adapted to operate the IMD in a first mode 1166, a second mode 1167and an Nth mode 1168. The illustration further includes a representationof a triggering event 1169, which can be an automatic event 1170 and/ora patient-actuated event 1171 such as a magnet moved proximate to a reedswitch or a patient-actuated programmer. Examples of automatictriggering events include a detected device change such as a detectedelectrode failure, an End Of Life (EOL) determination for a battery topower the device, a detected lead failure, an environmental change likea detected electrical interference that is capable of interfering withthe sensed signal or the application of another therapy capable ofinterfering with the sensed signal. Automatic triggering events can alsoinclude a detected physiologic change such as a detected change in heartrate, a detected arrhythmia, a detected change in a respiratory rate, adetected change in neural traffic, a detected change in blood pressure,and a detected change in activity. Automatic triggering events can alsobe based on a timer or clock, such as a device with a controller andtimer adapted to follow a circadian rhythm when switching modes. Theillustration also includes an enable signal 1172 connected to thecontroller to enable a mode of operation via a switch 1173. Thetriggering event is adapted to control the switch 1173 to selectivelyenable a mode of operation by the controller 1104. The illustratedresponsive relationship can be performed in hardware, software, or acombination thereof.

FIG. 12 illustrates an embodiment of a controller 1204 capable ofswitching modes within a set of operation modes 1274, a set ofstimulation site modes 1275, and a set of feedback modes 1276. Withrespect to the set of operation modes 1274, the illustrated controller1204 is adapted to switch between or among two or more modes. An exampleof an application for switching modes within a set of operation modes1274 includes switching between therapy and diagnostic modes in responseto noise. Examples of modes within the set of operation modes 1274includes a stimulation and sensing mode 1277 in which closed-loop neuralstimulation is provided to neural target(s) based on sensed parameters,a stimulation mode 1278 in which open-loop neural stimulation isprovided to neural target(s), and a sensing mode 1279 in which neuralstimulation is not provided to neural target(s) but sensing processescontinue. Examples of sensed parameters include, but are not limited to,blood pressure, heart rate, and nerve traffic.

With respect to the set of stimulation site modes 1275, the illustratedcontroller 1204 is adapted to switch between or among two or morestimulation site modes. Examples of applications for switchingstimulation site modes 1275 includes switching between parasympatheticand sympathetic nerve stimulation to treat tachycardia-bradycardiasyndrome, switching from afferent to efferent stimulation, and changingthe dose of the neural stimulation therapy by changing the number ofstimulation sites. For example, the illustrated controller is adapted toswitch among a mode to stimulate a first stimulation site or sites 1280,a mode to stimulate a second stimulation site or sites 1281, and a modeto stimulate an Nth stimulation site or sites 1282.

With respect to the set of feedback modes 1276, the illustratedcontroller is adapted to switch among sensing site modes 1283 and toswitch among sensed parameter and/or composite parameter modes 1284.Composite parameters are parameters based on two or more otherparameters. Examples of applications for switching among sensing sitemodes 1283 includes recording parasympathetic or sympathetic traffic,recording afferent or efferent traffic, and switching from atrial toventricular rhythm monitoring, Examples of applications for switchingamong sensed parameter/composite parameter modes 1284 include detectingshort-term brief events such as an impulse burst versus a time-averagedlong-term signal trend, and detecting impulse duration versus impulsemagnitude. The illustrated controller is adapted to switch among a firstsite 1285, a second site 1286 and an Nth site 1287 from which to providesensing for a feedback signal, and is also adapted to switch among afirst sensed parameter 1288, a second sensed parameter 1289 and an Nthsensed parameter 1290. Thus, although the sensing site may not change, adifferent parameter can be detected.

FIG. 13 illustrates an embodiment of a controller 1304 capable ofswitching modes within a set of operation modes 1374, a set ofstimulation site modes 1375, a set of feedback modes 1376, and a set oftherapy modes 1391. Examples of modes 1374, 1375 and 1376 are providedin FIG. 12 at 1274, 1275 and 1276. With respect to the set of therapymodes 1391, the illustrated controller 1304 is adapted to switch betweenor among two or more modes. Examples of modes within the set of therapymodes includes a neural stimulation therapy mode 1392, a cardiac rhythmmanagement and/or cardiac resynchronization therapy (CRM/CRT) mode 1393,a neural stimulation and CRM therapy mode 1394, a drug therapy mode1395, a neural stimulation and drug therapy mode 1396, a CRM/CRT anddrug therapy mode 1397, and a neural stimulation, CRM/CRT and drugtherapy mode 1398. An example of a neural stimulation mode 1392 includesan anti-remodeling, vagal nerve stimulation therapy. An example of aCRM/CRT therapy 1393 includes a resynchronization therapy for a heartfailure patient to improve the pumping function of the left ventricle.Examples of a neural stimulation and a CRM/CRT therapy 1394 include avagal nerve stimulation therapy and anti-tachycardia pacing to terminatearrhythmia, and vagal nerve stimulation in anticipation of adefibrillation shock to reduce the defibrillation threshold. An exampleof a drug therapy mode 1395 includes an angiogenic growth factor releaseto treat ischemia, An example of a neural stimulation and a drug therapymode 1396 includes vagal nerve stimulation and delivery of an angiogenicdrug to promote cardiac muscle repair after a myocardial infarction. Anexample of a CRM/CRT and drug therapy includes pacing to unload a regionof a heart damaged by a myocardial infarction such that the damagedheart, region works less and delivery of an angiogenic drug to promotecardiac muscle repair. An example of a neural stimulation, CRM/CRM anddrug therapy 1398 includes vagal nerve stimulation, pacing to unload aregion of a heart damaged by a myocardial infarction, and delivery of anangiogenic drug to prevent post myocardial infarction remodeling.

One of ordinary skill in the art will understand that, the modules andother circuitry shown and described herein can be implemented usingsoftware, hardware, and combinations of software and hardware. As such,the illustrated modules and circuitry are intended to encompass softwareimplementations, hardware implementations, and software and hardwareimplementations.

The methods illustrated in this disclosure are not intended to beexclusive of other methods within the scope of the present subjectmatter. Those of ordinary skill in the art will understand, upon readingand comprehending this disclosure, other methods within the scope of thepresent subject matter. The above-identified embodiments, and portionsof the illustrated embodiments, are not necessarily mutually exclusive.These embodiments, or portions thereof, can be combined. With referenceto FIG. 5, for example, some embodiments use sensed activity, such assensed neural activity, in a neural stimulation device to switch modesfor a CRM device. The sensed data in the neural stimulation device canbe used to alter the mode, rate, AV delay, VV delay, tachyarrhythmiaparameters, and various combinations thereof. Some embodiments allowdata sensed in a CRM device to mode switch a neural stimulation device.

In various embodiments, the methods provided above are implemented as acomputer data signal embodied in a carrier wave or propagated signal,that represents a sequence of instructions which, when executed by aprocessor cause the processor to perform the respective method. Invarious embodiments, methods provided above are implemented as a set ofinstructions contained on a computer-accessible medium capable ofdirecting a processor to perform the respective method. In variousembodiments, the medium is a magnetic medium, an electronic medium, oran optical medium.

Although specific embodiments have been illustrated and describedherein, it will be appreciated by those of ordinary skill in the artthat any arrangement which is calculated to achieve the same purpose maybe substituted for the specific embodiment shown. This application isintended to cover adaptations or variations of the present subjectmatter. It is to be understood that the above description is intended tobe illustrative, and not restrictive. Combinations of the aboveembodiments as well as combinations of portions of the above embodimentsin other embodiments will be apparent to those of skill in the art uponreviewing the above description. The scope of the present subject mattershould be determined with reference to the appended claims, along withthe full scope of equivalents to which such claims are entitled.

1. (canceled)
 2. An implantable system, comprising: at least one nervetraffic sensor configured to sense nerve traffic; memory including setsof programmed instructions stored therein to operate the implantablesystem to respond to a sensed triggering event by switching from a firstsensing mode for nerve traffic sensing to a second sensing mode fornerve traffic sensing; and a controller connected to the memory and theat least one sensor, the controller configured to execute the programmedinstructions in the memory to operate the implantable system to respondto the sensed triggering event using the sensed nerve traffic byswitching from the first sensing mode to the second sensing mode,wherein the implantable system is configured to sense a first parameterin the first sensing mode and to sense a second parameter in the secondsensing mode, wherein the first and the second parameters are different.3. The system of claim 2, wherein the sensed triggering event isdetermined using the sensed nerve traffic.
 4. The system of claim 2,wherein the implantable system is configured to sense a first compositephysiologic parameter in the first sensing mode and to sense a secondcomposite physiologic parameter in the second sensing mode.
 5. Thesystem of claim 2, wherein the implantable system is configured to sensean impulse width of the sensed nerve traffic in one of the first orsecond sensing modes, and sense an impulse magnitude of the sensed nervetraffic in another of the first or second sensing modes.
 6. The systemof claim 2, wherein the implantable system is configured to sense aburst of nerve traffic in one of the first or second sensing modes, andsense a trend of the nerve traffic in another of the first or secondsensing modes.
 7. The system of claim 2, further comprising stimulationcircuitry configured to use at least one electrode to provide at leastone neural stimulation therapy to at least one neural stimulation targetusing the at least one electrode.
 8. The system of claim 2, wherein thesystem is configured to use the at least one nerve traffic sensor tosense at least one of: an impulse magnitude, an impulse width, a nervetraffic burst, or a nerve traffic trend.
 9. The system of claim 2,wherein the implantable system is configured to sense nerve traffic at afirst sensing site in the first sensing mode, and sense nerve traffic ata second sensing site in the second sensing mode, wherein the first andsecond sensing sites are different.
 10. The system of claim 2, whereinthe implantable system is configured to deliver a therapy when operatingin a first sensing mode and not deliver the therapy when operating inthe second sensing mode.
 11. The system of claim 10, wherein the therapyincludes a neural stimulation therapy.
 12. The system of claim 10,wherein the therapy includes a drug therapy.
 13. The system of claim 2,wherein the sensed triggering event includes sensed activity, sensedblood pressure, sensed heart rate, or sensed respiration.
 14. A methodimplemented using an implantable system that includes at least one nervetraffic sensor, a memory, and a controller connected to the memory andthe at least one sensor, the method including: sensing nerve trafficusing the at least one nerve traffic sensor; and using the controller toexecute programmed instructions in the memory to operate the implantablesystem to respond to a sensed triggering event by switching from a firstsensing mode for nerve traffic sensing to a second sensing mode fornerve traffic sensing, wherein a first parameter is sensed in the firstsensing mode and a second parameter is sensed in the second sensingmode, wherein the first and the second parameters are different.
 15. Themethod of claim 14, wherein the sensed triggering event is determinedusing the sensed nerve traffic.
 16. The method of claim 14, wherein thesensed triggering event is determined using the sensed nerve traffic.17. The method of claim 14, wherein the implantable system is configuredto sense a first composite physiologic parameter in the first sensingmode and to sense a second composite physiologic parameter in the secondsensing mode.
 18. A non-transitory machine-readable medium includinginstructions, which when executed by a machine, cause the machine to:sense nerve traffic using at least one nerve traffic sensor; provide atleast a first sensing mode for nerve traffic sensing and a secondsensing mode for nerve traffic sensing, and switch the sensing modes inresponse to a sensed triggering event, wherein a first parameter issensed in the first sensing mode and a second parameter is sensed in thesecond sensing mode, wherein the first and the second parameters aredifferent.
 19. The non-transitory machine-readable medium of claim 18,wherein the sensed triggering event is determined using the sensed nervetraffic.
 20. The non-transitory machine-readable medium of claim 18,wherein the implantable system is configured to sense nerve traffic at afirst sensing site in the first sensing mode, and sense nerve traffic ata second sensing site in the second sensing mode, wherein the first andsecond sensing sites are different.
 21. The non-transitorymachine-readable medium of claim 18, wherein the implantable system isconfigured to deliver a therapy when operating in a first sensing modeand not deliver the therapy when operating in the second sensing mode,and wherein the therapy includes a neural stimulation therapy or a drugtherapy.